Prostaglandin (PG)-like substances are produced by the cell from precursor fatty acids. Trauma or extracellular effectors influence their synthesis. These molecules then effect cell behavior in the vicinity of their production. They are generally unstable or quickly metabolized in the organism. Accumulating evidence suggest that the PG-like substances participate in the modulation of cell division, at least in part via the cyclic nucleotide system. The results we have obtained thus far suggest that an alteration in the synthesis of the PGs as well as their effect on certain metabolic parameters of the cell i.e., adenyl cyclase activity may be contributing, during cell senescence, to the reduction in cell number of confluence and finally the inability of late passage human diploid fibroblasts (HDF) to undergo further cell proliferation. We therefore propose to: (1) investigate the role of PG-like molecules in the growth of HDF; (2) determine the production of PGs during the different phases of cell growth including at cell confluence; (3) determine whether the production of PGs alters as cells senescence; (4) determine if the effect of the PGs on cell growth alters in senescing cells; (5) determine if and how the interaction amonth the PGs, the cyclic nucleotide systems and other metabolic parameters at or near the cell surface can bring about decreases in cell number and the cessation of cell growth during cell senesence.